The S100B Protein: A Multifaceted Pathogenic Factor More Than a Biomarker

Abstract

S100B is a calcium-binding protein mainly concentrated in astrocytes in the nervous system. Its levels in biological fluids are recognized as a reliable biomarker of active neural distress, and more recently, mounting evidence points to S100B as a Damage-Associated Molecular Pattern molecule, which, at high concentration, triggers tissue reactions to damage. S100B levels and/or distribution in the nervous tissue of patients and/or experimental models of different neural disorders, for which the protein is used as a biomarker, are directly related to the progress of the disease. In addition, in experimental models of diseases such as Alzheimer's and Parkinson's diseases, amyotrophic lateral sclerosis, multiple sclerosis, traumatic and vascular acute neural injury, epilepsy, and inflammatory bowel disease, alteration of S100B levels correlates with the occurrence of clinical and/or toxic parameters. In general, overexpression/administration of S100B worsens the clinical presentation, whereas deletion/inactivation of the protein contributes to the amelioration of the symptoms. Thus, the S100B protein may be proposed as a common pathogenic factor in different disorders, sharing different symptoms and etiologies but appearing to share some common pathogenic processes reasonably attributable to neuroinflammation.

Keywords: S100B protein; pathogenic factor.

Figure 1

Schematic representation of effects induced by extracellular astrocytic S100B. At nanomolar concentrations, S100B does not impact the homeostasis of microglia. In contrast, when S100B reaches micromolar concentrations, microglia rapidly activate NF-κB-dependent transcription and exhibit pro-inflammatory phenotypes. Negative regulation of extracellular S100B can reprogram microglia from inflammation towards homeostasis via suppression of NF-κB signaling.